U.S. patent number 6,805,703 [Application Number 09/954,185] was granted by the patent office on 2004-10-19 for protective membrane for reconfiguring a workpiece.
This patent grant is currently assigned to SciMed Life Systems, Inc.. Invention is credited to David McMorrow.
United States Patent |
6,805,703 |
McMorrow |
October 19, 2004 |
Protective membrane for reconfiguring a workpiece
Abstract
A method of protecting the coating on a reconfigurable coated
workpiece having a first end and a second end is provided in one
embodiment of the present invention. This embodiment includes
providing an encasing hollow deformable membrane, positioning the
first end of the reconfigurable coated workpiece adjacent to an
entrance orifice of the membrane, enlarging the entrance orifice
and the inside cavity of the membrane, inserting the reconfigurable
coated workpiece into the enlarged entrance orifice and into the
inside cavity and decreasing the size of the inside cavity of the
membrane until an inside surface of the cavity contacts the coating
of the workpiece.
Inventors: |
McMorrow; David (Galway,
IE) |
Assignee: |
SciMed Life Systems, Inc.
(Maple Grove, MN)
|
Family
ID: |
25495058 |
Appl.
No.: |
09/954,185 |
Filed: |
September 18, 2001 |
Current U.S.
Class: |
623/1.11;
623/1.15; 623/1.46 |
Current CPC
Class: |
A61F
2/95 (20130101); A61F 2/82 (20130101) |
Current International
Class: |
A61F
2/06 (20060101); A61F 002/06 () |
Field of
Search: |
;606/194,198 ;623/1
;425/517 |
References Cited
[Referenced By]
U.S. Patent Documents
Foreign Patent Documents
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|
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|
0732087 |
|
Sep 1996 |
|
EP |
|
0920843 |
|
Jun 1999 |
|
EP |
|
Primary Examiner: Reip; David O.
Assistant Examiner: Sam; Charles H.
Attorney, Agent or Firm: Kenyon & Kenyon
Claims
What is claimed is:
1. A method of protecting the coating on a reconfigurable coated
workpiece having a first end and a second end, the method
comprising: providing an encasing hollow deformable membrane, the
membrane having an entrance orifice, the membrane having an inside
cavity; positioning the first end of the reconfigurable coated
workpiece adjacent to the entrance orifice of the membrane;
enlarging the entrance orifice and the inside cavity of the
membrane; inserting the reconfigurable coated workpiece into the
enlarged entrance orifice and into the inside cavity; and
decreasing the size of the inside cavity until an inside surface of
the inside cavity contacts the coating of the workpiece.
2. The method of claim 1 wherein the workpiece is a medical
implant.
3. The method of claim 1 further comprising: reconfiguring the
reconfigurable coated workpiece from a first configuration to a
second configuration.
4. The method of claim 3 wherein reconfiguring the reconfigurable
coated workpiece includes applying a compressive force to an
outside surface of the membrane.
5. The method of claim 1 wherein enlarging the entrance orifice and
the inside cavity includes injecting a pressurized fluid into the
membrane.
6. The method of claim 3 wherein the reconfigurable coated
workpiece is carried on a distal portion of a carrier device.
7. The method of claim 6 wherein the reconfigurable coated
workpiece is a coated stent and wherein the carrier device is a
catheter.
8. The method of claim 7 wherein the cross-section of the inside
cavity of the membrane in its resting non-expanded state is smaller
than the cross-section of the coated stent in the second
configuration.
9. The method of claim 1 wherein the coating of the workpiece
includes a polymer carrying a therapeutic.
10. The method of claim 1 wherein the membrane is tube-like and
also contains an exit orifice.
11. The method of claim 1 wherein the membrane includes compounds
selected from a group consisting of latex, silicone, polyurethane,
chloroprene and nitrile.
12. The method of claim 10 wherein the membrane has a thickness of
about 0.3 mm.
13. The method of claim 1 wherein the reconfigurable coated
workpiece is either a stent, a graft, a stent graft or a vena cava
filter.
14. The method of claim 1 further comprising: placing a protective
covering around an outside surface of the membrane.
15. The method of claim 14 wherein the protective covering is a
monofilament nylon braided sleeve.
16. The method of claim 1 further comprising: providing a coated
medical implant as the coated workpiece comprising: a frame, the
frame expandable from a first configuration to a second
configuration, the frame having external coating, the coating
having a deliverable therapeutic.
17. The method of claim 1 further comprising: providing a hollow
reconfiguration chamber comprising a brace sized to support and in
contact with an entrance orifice of the hollow deformable membrane
having an internal surface, the internal surface of the hollow
deformable membrane in fluid communication with a source of
pressurized fluid.
18. The method of claim 1 further comprising: a means for
supporting and holding open an entrance orifice of the hollow
deformable membrane, the entrance orifice positioned to accept he
reconfigurable coated workpiece, the entrance orifice in fluid
communication with a source of pressurized fluid, the hollow
deformable membrane having an internal cavity cross-section that is
smaller than the cross-section of the reconfigurable coated
workpiece in a compressed state.
19. The method of claim 7, wherein the stent comprising: a metallic
frame, the frame expandable from a first position to a second
position; a polymeric layer coating at least a portion of the
metallic frame, the polymeric layer carrying a therapeutic agent;
and the encasing hollow deformable membrane surrounding the polymer
layer, an internal surface of the encasing hollow deformable layer
in contact with the polymeric layer.
20. The method of claim 1 wherein the encasing hollow deformable
membrane is in the shape of a sleeve.
21. The method of claim 1 wherein the entrance orifice of membrane
contains a zip chord.
22. The method of claim 1 wherein the entrance orifice of the
hollow deformable membrane is its only orifice.
23. The method of claim 1 wherein the hollow deformable membrane
has a thickness substantially between 0.3 mm and 0.6 mm.
24. The method of claim 1 wherein the hollow deformable membrane
defines a sleeve having a first orifice and a second orifice.
Description
FIELD OF THE INVENTION
The present invention regards protecting a workpiece during its
manufacture or reconfiguration. More specifically the present
invention regards reducing the probability of damaging a coating on
a workpiece during the workpiece's manufacture or reconfiguration
by using a protective membrane.
BACKGROUND
Articles of manufacture are regularly coated for numerous and
varying reasons. For example, they may be coated to protect them
from the intrusive handling they can be subjected to during their
manufacture and to protect them from the severe environmental
conditions they can encounter after they are manufactured. In
either circumstance, as well as in others, damage to the coating of
a workpiece, resulting from the handling, mishandling or
reconfiguration of the workpiece, is an unwanted result.
When the coating of a workpiece becomes scratched or otherwise
damaged during its manufacture, the scratches can promote the
deterioration of not only the coating but also the workpiece itself
by exposing the workpiece's surface to its surroundings. For
instance, should the workpiece be employed in a corrosive
environment, its errantly exposed surface would be more vulnerable
to corrosion than if its coating were completely intact.
Moreover, the scratches and inconsistencies in the coating of a
workpiece may also reduce the effectiveness of the finished
product. For example, should the coating be used to uniformly
deliver some type of releasable substance, inconsistencies in the
coating can foster uneven and non-homogeneous delivery of the
releasable substance to the deployed product's final
surroundings.
An expandable coated stent is one specific example of the coated
workpieces described above. Expandable stents are tube-like medical
devices designed to support the inner walls of a vessel or lumen
within the body of a patient. These stents are typically positioned
within a targeted lumen of the body and then expanded to provide
internal support for the lumen. These stents may be self-expanding
or, alternatively, may require external forces to expand them. In
either case they are typically deployed through the use of a
catheter of some kind. These catheters typically carry the stents
at their distal end.
Due to the interaction of the stent with the inner walls of the
lumen, stents have been coated to enhance their effectiveness.
These coatings may, among other things, be designed to facilitate
the acceptance of the stent into its applied surroundings or to
facilitate the delivery of therapeutic to the lumen and its
surroundings. When the coating is haphazardly applied or has
somehow been removed during the stent's manufacture, both the
stent's useable life span and its effectiveness can be reduced.
The coatings on these stent may be applied at various times during
its life cycle including during its manufacture, during its
placement onto the distal end of the delivery catheter, and
contemporaneous with the medical procedure being performed. At each
of these times the coating may be at risk of being scratched,
damaged or otherwise removed from the surface of the stent. For
example, during their manufacture, stents are often crimped onto
the distal end of the delivery catheter. During this crimping the
mechanical arms of a crimper may come in contact with the coating
of the stent as the arms act to reduce the diameter of the stent.
This compressive contact can scratch, indent, wipe-off or otherwise
breach the integrity of the coating.
SUMMARY OF THE INVENTION
A method of protecting the coating on a reconfigurable coated
workpiece having a first end and a second end is provided in one
embodiment of the present invention. This embodiment includes
providing an encasing hollow deformable membrane, positioning the
first end of the reconfigurable coated workpiece adjacent to an
entrance orifice of the membrane, enlarging the entrance orifice
and the inside cavity of the membrane, inserting the reconfigurable
coated workpiece into the enlarged entrance orifice and into the
inside cavity, and decreasing the size of the inside cavity of the
membrane until an inside surface of the cavity contacts the coating
of the workpiece.
A system for delivering a coated reconfigurable medical implant to
a target site is also provided in an alternative embodiment of the
present invention. A system in accord with this embodiment includes
a carrier device and a medical implant covered in a protective
membrane wherein the medical implant is located at the distal end
of the carrier device on an implant carrying region.
A medical stent in accord with another embodiment is also provided.
A stent in accord with this embodiment may include a metallic frame
that may be expandable from a first position to a second position,
a polymeric layer coating at least a portion of the metallic frame,
and an encasing hollow deformable membrane surrounding the polymer
layer.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side view of a coated workpiece that was manufactured
without a protective membrane in place.
FIG. 2 is a side view of a coated workpiece that was manufactured
in accord with an embodiment of the present invention.
FIG. 3 is a side view of a coated implant that has an encasing
hollow deformable membrane surrounding it in accord with an
alternative embodiment of the present invention.
FIG. 4 is a cross-sectional view taken along line IV--IV of FIG.
3.
FIG. 5 is a side view of the coated implant of FIG. 3 after it has
been reconfigured in accord with an alternative embodiment of the
present invention.
FIG. 6 is a cross-sectional view taken along line VI--VI of FIG.
5.
FIG. 7 is a side view of an uncrimped stent on a catheter prior to
its insertion into an encasing hollow deformable membrane in accord
with another alternative embodiment of the present invention.
FIG. 8 is a side view of the uncrimped stent of FIG. 7 after it has
been inserted into the deformable membrane in accord with another
alternative embodiment of the present invention.
FIG. 9 is a side view of the uncrimped stent of FIGS. 7-8 after the
deformable membrane has been placed around it in accord with
another alternative embodiment of the present invention.
FIG. 10 is a side view of the covered stent of FIGS. 7-9 prior to
its insertion into a crimping chamber in accord with another
alternative embodiment of the present invention.
FIG. 11 is a side view of a covered implant prior to its insertion
into a braided sleeve in accord with another alternative embodiment
of the present invention.
FIG. 12 is a side view of an implant prior to its insertion into an
encasing hollow deformable membrane in accord with another
alternative embodiment of the present invention.
DETAILED DESCRIPTION
FIG. 1 is a side view of a coated workpiece 10 that was
manufactured without the benefit of a protective membrane. As can
been seen, the coating 12 of the workpiece haphazardly covers the
workpiece 10 and in some areas 11 the workpiece 10 is not covered
at all. The missing coating 12 from these removed areas 11 may have
been errantly removed during various manufacturing steps and may
have even been deposited on both the machinery and the personnel
that handled the workpiece during these steps.
FIG. 2 is a side view of a coated workpiece 20 that was
manufactured using a protective deformable membrane in accord with
one embodiment of the present invention. As can be seen, the
workpiece 20 has maintained most, if not all of its protective
coating 21 with only a few depressions 22 evident on the
workpiece's surface. With more of the coating 21 intact the
workpiece 20 may be better suited to perform its desired function
after its is deployed for its ultimate use. Moreover, by employing
an encasing membrane to protect the coating 21 during the
manufacture of the workpiece 20 the loads placed on the workpiece
may be more evenly distributed across the coating 21 and the
coating 21 may be less susceptible to contaminating everything that
comes in contact with it.
FIG. 3 is a side view of a coated implant 35, having a coating 32
that may be protected by an encasing membrane in accord with an
alternative embodiment of the present invention. The coated implant
35 in this embodiment, which is comprised of the implant 30 defined
by its frame 36, may be covered with a coating 32 that is in turn
surrounded by an encasing hollow deformable membrane 31. This
encasing deformable membrane 31 may be used to protect the coating
32 during the crimping of the implant 30, during its other
manufacturing steps, and during its subsequent handling.
During the crimping of an implant two goals are in conflict, high
forces are desired to adequately secure the implant to the implant
carrying region of a catheter or other carrier device while reduced
forces are desired to prevent the smearing or removal of the
coating on the implant 30. By using a protective membrane 31 around
the coating the damage caused by the compressive forces necessary
to crimp the implant may be reduced. Moreover, by encasing a coated
implant in a membrane 31 the smearing or other errant removal of
the coating may be diminished by the presence of the membrane
31.
In its resting state the deformable membrane 31 may have an inner
diameter that is smaller than the outer diameter of the implant 30.
Consequently, the deformable membrane 31 in this embodiment should
be enlarged in order to place the coated implant 30 into it. By
having the deformable membrane 31 in a state of expansion while it
encases the implant 30 the retroactive forces, to return the
deformable membrane 31 to its original configuration, can help
maintain the positioning of the membrane 31 on the implant 30
during its subsequent handling and use. Alternatively, in a
different embodiment, rather than using pure compressive forces to
retain the membrane around the implant 30, the deformable membrane
may be ribbed or folded or otherwise configured to facilitate its
retention onto the implant 30.
FIG. 4 is a cross-sectional view taken along line IV--IV of FIG. 3.
As can be seen, the encasing hollow deformable membrane 31 of the
implant 30 is circular and completely encases the implant 30 and
its coating 32. The implant 30 in this configuration has not yet
been crimped onto a catheter or other carrier device.
FIG. 5 is a side view of the implant 30 after it has been crimped.
It is evident in FIG. 5 that the diameter of the implant 30 has
been reduced during the crimping process. During this crimping
process forces in the direction of arrows 51 have been exerted on
the membrane 31 to reduce the diameter of the implant 30. As is
evident, the coating 32 has remained intact during this step.
FIG. 6 is a cross-sectional view taken along line VI--VI of FIG. 5.
When FIG. 6 is compared to FIG. 4 the reduction in diameter of the
implant 30 is clearly evident.
FIG. 7 is a side view of a system that may be used in accord with
an alternative embodiment of the present invention. In FIG. 7 the
carrier device 74 may carry an implant 73 on an implant retention
region near its distal end. This implant 73 may be held in place by
sox 75 and may be coated with coating 79. The implant 73 and the
carrier device 74 may be stored within hypo-tube 76 and may be
extended out of the hypo-tube 76 during the manufacturing process,
as shown by arrow 77, in order to place the membrane 72 around it.
The encasing hollow deformable membrane 72 may be supported or
stretched open by one end of an encasing cage 71. This encasing
cage 71 may be a wire cage sized to hold the membrane open, it may
also be a clear tube or any other device adapted to hold the
entrance orifice of the membrane 72 open during the manufacturing
process.
During the manufacturing process, the carrier device 74 may be
inserted into the entrance orifice of the membrane 72 such that the
membrane 72 covers both sox 75 and the implant 73. The membrane 72
may then be slid off of the cage 71 so that the membrane will
completely encase the implant and the sox. Then, after the membrane
72 has been slid off of the cage 71, the carrier device may be
retracted from the cage 71, now with its implant covered with the
protective membrane 72.
FIG. 8 is another side sectional view of the carrier device 74 and
the encasing membrane 72 of the embodiment of FIG. 7, this time
during the actual covering of the implant 73. In this step, as
described above, the hypo-tube 76 has been inserted into the
opening of the encasing cage 71 and the encasing hollow deformable
membrane 72. Once the hypo-tube has been inserted into this opening
a compressed fluid may be injected within a lumen 81 of the
hypo-tube in order to inflate the membrane 72. Then, once the
membrane is inflated, the distal end of the carrier device 74 may
be urged into the membrane 72. The hypo-tube 76 may then be pulled
away from the cage 71, stopping the flow of compressed air into the
membrane 72 and allowing the membrane to relax and encircle the
implant 73. The entrance orifice of the membrane 72 may also be
released from the cage 71 at this point to allow the membrane to
completely encircle the implant.
FIG. 9 shows a side view of the carrier device 74 after the
membrane 72 has been released from the cage 71 as described above.
As is evident in FIG. 9 the hypo-tube 76 is no longer inserted into
the cage 71 and the implant 73 is now completely covered by the
membrane 72. This implant may now be removed from the case 71 and
may be processed or handled in subsequent steps with the benefit of
the protective membrane.
FIG. 10 shows a side view of the carrier device of FIGS. 7-9 after
the implant has been covered and prior to its insertion into a
crimping device 100. This crimping device may be a hand held device
or a mechanical device that may reduce the diameter of the implant
73 to more firmly secure it to the implant retention region located
at the distal end of the carrier device 76. Once the implant has
been crimped, the membrane 72 may be removed immediately or it may
remain on the implant 73 until just prior to its use by a
practitioner. Alternatively, rather than behaving solely as a
crimping mechanism, this device 100 may complete both steps by
first applying the membrane and then crimping the implant.
FIG. 11 shows a side view of another alternative embodiment of the
present invention. In this alternative embodiment an implant device
112 has an implant covered in a membrane 110 located at the
device's 112 distal end. The membrane 110 in this embodiment is
shaped like a sleeve and, therefore, has an exit orifice 113. In
this embodiment a supplemental cover, here a nylon braided sleeve
111, may be placed over the membrane 110 to further protect the
membrane during subsequent manufacturing and handling steps.
FIG. 12 is a side view of an implant 123 prior to its insertion
into an encasing membrane 126 in accord with another alternative
embodiment of the present invention. In this embodiment, rather
than having compressed air injected through the hypo-tube, two
nozzles 121 are positioned near the cage 125 entrance such that
they may inject pressurized fluid into entrance orifice of the
membrane 126 stretched open by the cage 125. This cage 125 may also
contain a brace 122 within it to prevent the membrane 126 from
being over-inflated during the process. Therefore, in use, the
membrane may be inflated by the nozzles to allow the implant 123 to
be inserted into it. Once the implant has been inserted into the
membrane, the membrane may then be slid off of the cage. The
carrier device 124, now carrying the implant, may, then, be removed
from the cage 125 for subsequent use and handling. Alternatively,
rather than injecting fluid to inflate the membrane, the nozzles
may be situated behind the membrane and may be used to create a
vacuum, thereby drawing the membrane into the cage to enlarge
it.
In each of the above embodiments, once the workpiece is ready to be
employed for its intended use, or at any other time deemed
appropriate by the user, the protective membrane can be removed.
The membrane may be removed by inflating or alternatively through
some destructive method including a zip cord that will sever the
membrane when it is pulled.
A protective membrane as employed in the various embodiments of the
present invention can be manufactured from a number of materials,
including latex, silicone, polyurethane, chloroprene or nitrile. It
may also have a thickness preferably between 0.3 mm and 0.6 mm and
contain materials that are flexible and allow for the transmission
of forces to the workpiece during the workpiece's manufacture. In
one embodiment, the membrane is a tube with a single opening while
in another embodiment the membrane is a sleeve with openings on
both ends.
The range of medical implants that may be protected by these
membranes include: expandable and self-expanding stents, balloon
catheters, vena-cava filters, aneurysm coils, stent-grafts, a-v
shunts, anglo-catheters, and PICC's. Moreover, the coatings
employed may contain paclitaxel as well as others therapeutics,
which include, for example: pharmaceutically active compounds,
proteins, cells, oligonucleotides, ribozymes, anti-sense
oligonucleotides, DNA compacting agents, gene/vector systems (i.e.,
any vehicle that allows for the uptake and expression of nucleic
acids), nucleic acids (including, for example, recombinant nucleic
acids; naked DNA, cDNA, RNA; genomic DNA, cDNA or RNA in a
non-infectious vector or in a viral vector and which further may
have attached peptide targeting sequences; antisense nucleic acid
(RNA or DNA); and DNA chimeras which include gene sequences and
encoding for ferry proteins such as membrane translocating
sequences ("MTS") and herpes simplex virus-1 ("VP22")), and viral,
liposomes and cationic and anionic polymers and neutral polymers
that are selected from a number of types depending on the desired
application. Non-limiting examples of virus vectors or vectors
derived from viral sources include adenoviral vectors, herpes
simplex vectors, papilloma vectors, adeno-associated vectors,
retroviral vectors, and the like. Non-limiting examples of
biologically active solutes include anti-thrombogenic agents such
as heparin, heparin derivatives, urokinase, and PPACK
(dextrophenylalanine proline arginine chloromethylketone);
antioxidants such as probucol and retinoic acid; angiogenic and
anti-angiogenic agents and factors; agents blocking smooth muscle
cell proliferation such as rapamycin, angiopeptin, and monoclonal
antibodies capable of blocking smooth muscle cell proliferation;
anti-inflammatory agents such as dexamethasone, prednisolone,
corticosterone, budesonide, estrogen, sulfasalazine, acetyl
salicylic acid, and mesalamine; calcium entry blocker such as
verapamil, diltiazem and nifedipine;
antineoplastic/antiproliferative/anti-mitotic agent such as
paclitaxel, 5-fluorouracil, methotrexate, doxorubicin,
daunorubicin, cyclosporine, cisplatin, vinbiastine, vincristine,
epothilones, endostatin, angiostatin and thymidine kinase
inhibitors; antimicrobials such as triclosan, cephalosporins,
aminoglycosides, and nitrofurantoin; anesthetic agents such as
lidocaine, bupivacaine, and ropivacaine; nitric oxide (NO) donors
such as linsidomine, molsidomine, L-airginine, NO-protein adducts,
NO-carbohydrate adducts, polymeric or oligomeric NO adducts;
anti-coagulants such as D-Phe-Pro-Arg chloromethyl ketone, an RGD
peptide-containing compound, heparin, antithrombin compounds,
platelet receptor antagonists, anti-thrombin antibodies,
anti-platelet receptor antibodies, enoxaparin, hirudin, Warfarin
sodium, Dicumarol, aspirin, prostaglandin inhibitors, platelet
inhibitors and tick antiplatelet factors; vascular cell growth
promotors such as growth factors, growth factor receptor
antagonists, transcriptional activators, and translational
promotors; vascular cell growth inhibitors such as growth factor
inhibitors, growth factor receptor antagonists, transcriptional
repressors, translational repressors, replication inhibitors,
inhibitory antibodies, antibodies directed against growth factors
bifunctional molecules consisting of a growth factor and a
cytotoxin, bifimctional molecules consisting of an antibody and a
cytotoxin; cholesterol-lowering agents; vasodilating agents; agents
which interfere with endogeneus vascoactive mechanisms; survival
genes which protect against cell death, such as anti-apoptotic
Bcl-2 family factors and Akt kinase; and combinations thereof.
Cells can be of human origin (autologous or allogenic) or from an
animal source (xenogeneic), genetically engineered if desired to
deliver proteins of interest at the injection site. The delivery
medium is formulated as needed to maintain cell function and
viability. Any modifications are routinely made by one skilled in
the art.
Polynucleotide sequences useful in practice of the invention
include DNA or RNA sequences having a therapeutic effect after
being taken up by a cell. Examples of therapeutic polynucleotides
include anti-sense DNA and RNA; DNA coding for an antisense RNA; or
DNA coding for tRNA or rRNA to replace defective or deficient
endogenous molecules. The polynucleotides of the invention can also
code for therapeutic proteins or polypeptides. A polypeptide is
understood to be any translation product of a polynucleotide
regardless of size, and whether glycosylated or not. Therapeutic
proteins and polypeptides include as a primary example, those
proteins or polypeptides that can compensate for defective or
deficient species in an animal, or those that act through toxic
effects to limit or remove harmful cells from the body. In
addition, the polypeptides or proteins that can be injected, or
whose DNA can be incorporated, include without limitation,
antigenic factors and other molecules competent to induce
angiogenesis, including acidic and basic fibroblast growth factors,
vascular endothelial growth factor, hif-1, epidermal growth factor,
transforming growth factor .alpha. and .beta., platelet-derived
endothelial growth factor, platelet-derived growth factor, tumor
necrosis factor .alpha., hepatocyte growth factor and insulin like
growth factor; growth factors; cell cycle inhibitors including CDK
inhibitors; anti-restenosis agents, including p15, p16, p18, p19,
p21, p27, p53, p57, Rb, nFkB and E2F decoys, thymidine kinase
("TK") and combinations thereof and other agents useful for
interfering with cell proliferation, including agents for treating
malignancies; and combinations thereof. Still other useful factors,
which can be provided as polypeptides or as DNA encoding these
polypeptides, include monocyte chemoattractant protein ("MCP-1"),
and the family of bone morphogenic proteins ("BMP's"). The known
proteins include BMP-2, BMP-3, BMP-4, BMP-5, BMP-6 (Vgr-1), BMP-7
(OP-1), BMP-8, BMP-9, BMP-10, BMP-11, BMP-12, BMP-13, BMP-14,
BMP-15, and BMP-16. Currently preferred BMP's are any of BMP-2,
BMP-3, BMP-4, BMP-5, BMP-6 and BMP-7. These dimeric proteins can be
provided as homodimers, heterodimers, or combinations thereof,
alone or together with other molecules. Alternatively or, in
addition, molecules capable of inducing an upstream or downstream
effect of a BMP can be provided. Such molecules include any of the
"hedgehog" proteins, or the DNA's encoding them.
These therapeutic agents can be used, for example, in any
application for treating, preventing, or otherwise affecting the
course of a disease or tissue or organ dysfunction. For example,
the methods of the invention can be used to induce or inhibit
angiogenesis, as desired, to prevent or treat restenosis, to treat
a cardiomyopathy or other dysfunction of the heart, for treating
Parkinson's disease or a stroke or other dysfunction of the brain,
for treating cystic fibrosis or other dysfunction of the lung, for
treating or inhibiting malignant cell proliferation, for treating
any malignancy, and for inducing nerve, blood vessel or tissue
regeneration in a particular tissue or organ.
While various embodiments of the present invention are disclosed
above, other embodiments are also possible without straying from
the spirit and scope of the present invention.
* * * * *